PVA-Based Hydrogels Loaded with Diclofenac for Cartilage Replacement.

Polyvinyl alcohol (PVA) hydrogels have been widely studied for cartilage replacement due to their biocompatibility, chemical stability, and ability to be modified such that they approximate natural tissue behavior. Additionally, they may also be used with advantages as local drug delivery systems. However, their properties are not yet the most adequate for such applications. This work aimed to develop new PVA-based hydrogels for this purpose, displaying improved tribomechanical properties with the ability to control the release of diclofenac (DFN). Four types of PVA-based hydrogels were prepared via freeze-thawing: PVA, PVA/PAA (by polyacrylic acid (PAA) addition), PVA/PAA+PEG (by polyethylene glycol (PEG) immersion), and PVA/PAA+PEG+A (by annealing). Their morphology, water uptake, mechanical and rheological properties, wettability, friction coefficient, and drug release behavior were accessed. The irritability of the best-performing material was investigated. The results showed that the PAA addition increased the swelling and drug release amount. PEG immersion led to a more compact structure and significantly improved the material's tribomechanical performance. The annealing treatment led to the material with the most suitable properties: besides presenting a low friction coefficient, it further enhanced the mechanical properties and ensured a controlled DFN release for at least 3 days. Moreover, it did not reveal irritability potential for biological tissues.

Development of polycarbonate urethane-based materials with controlled diclofenac release for cartilage replacement.

Hydrogels are very promising human cartilage replacement materials since they are able to mimic its structure and properties. Besides, they can be used as platforms for drug delivery to reduce inflammatory postsurgical reactions. Polycarbonate urethane (PCU) has been used in orthopedic applications due to its long-term biocompatibility and bio-durability. In this work, PCU-based hydrogels with the ability to release an anti-inflammatory (diclofenac) were developed, for the first time, for such purpose. The materials were reinforced with different amounts of cellulose acetate (CA, 10%, 15%, and 25% w/w) or carbon nanotubes (CNT, 1% and 2% w/w) in order to improve their mechanical properties. Samples were characterized in terms of compressive and tensile mechanical behavior. It was found that 15% CA and 2% CNT reinforcement led to the best mechanical properties. Thus, these materials were further characterized in terms of morphology, wettability, and friction coefficient (CoF). Contrarily to CNTs, the addition of CA significantly increased the material's porosity. Both materials became more hydrophilic, and the CoF slightly increased for PCU + 15%CA. The materials were loaded by soaking with diclofenac, and drug release experiments were conducted. PCU, PCU + 15%CA and PCU + 2%CNT presented similar release profiles, being able to ensure a controlled release of DFN for at least 4 days. Finally, in vitro cytotoxicity tests using human chondrocytes were also performed and confirmed a high biocompatibility for the three studied materials.

Mineralization of Sialoliths Investigated by Ex Vivo and In Vivo X-ray Computed Tomography.

The fraction of organic matter present affects the fragmentation behavior of sialoliths; thus, pretherapeutic information on the degree of mineralization is relevant for a correct selection of lithotripsy procedures. This work proposes a methodology for in vivo characterization of salivary calculi in the pretherapeutic context. Sialoliths were characterized in detail by X-ray computed microtomography (µCT) in combination with atomic emission spectroscopy, Fourier transform infrared spectroscopy, X-ray diffraction, scanning electron microscopy, and transmission electron microscopy. Correlative analysis of the same specimens was performed by in vivo and ex vivo helical computed tomography (HCT) and ex vivo µCT. The mineral matter in the sialoliths consisted essentially of apatite (89 vol%) and whitlockite (11 vol%) with average density of 1.8 g/cm3. In hydrated conditions, the mineral mass prevailed with 53 ± 13 wt%, whereas the organic matter, with a density of 1.2 g/cm3, occupied 65 ± 10% of the sialoliths' volume. A quantitative relation between sialoliths mineral density and X-ray attenuation is proposed for both HCT and µCT.

Local Response of Sialoliths to Lithotripsy: Cues on Fragmentation Outcome.

Lithotripsy methods show relatively low efficiency in the fragmentation of sialoliths compared with the success rates achieved in the destruction of renal calculi. However, the information available on the mechanical behavior of sialoliths is limited and their apparently tougher response is not fully understood. This work evaluates the hardness and Young's modulus of sialoliths at different scales and analyzes specific damage patterns induced in these calcified structures by ultrasonic vibrations, pneumoballistic impacts, shock waves, and laser ablation. A clear correlation between local mechanical properties and ultrastructure/chemistry has been established: sialoliths are composite materials consisting of hard and soft components of mineralized and organic nature, respectively. Ultrasonic and pneumoballistic reverberations damage preferentially highly mineralized regions, leaving relatively unaffected the surrounding organic matter. In contrast, shock waves leach the organic component and lead to erosion of the overall structure. Laser ablation destroys homogeneously the irradiated zones regardless of the mineralized/organic nature of the underlying ultrastructure; however, damage is less extensive than with mechanical methods. Overall, the present results show that composition and internal structure are key features behind sialoliths' comminution behavior and that the organic matter contributes to reduce the therapeutic efficiency of lithotripsy methods.

Structure and growth of sialoliths: computed microtomography and electron microscopy investigation of 30 specimens.

Theories have been put forward on the etiology of sialoliths; however, a comprehensive understanding of their growth mechanisms is lacking. In an attempt to fill this gap, the current study has evaluated the internal architecture and growth patterns of a set of 30 independent specimens of sialoliths characterized at different scales by computed microtomography and electron microscopy. Tomography reconstructions showed cores in most of the sialoliths. The cores were surrounded by concentric or irregular patterns with variable degrees of mineralization. Regardless of the patterns, at finer scales the sialoliths consisted of banded and globular structures. The distribution of precipitates in the banded structures is compatible with a Liesegang-Ostwald phenomenon. On the other hand, the globular structures appear to arise from surface tension effects and to develop self-similar features as a result of a viscous fingering process. Electron diffraction patterns demonstrated that Ca- and P-based electrolytes crystallize in a structure close to that of hydroxyapatite. The organic matter contained sulfur with apparent origin from sulfated components of secretory material. These results cast new light on the mechanisms involved in the formation of sialoliths.